PMID- 16790241 OWN - NLM STAT- MEDLINE DCOM- 20061220 LR - 20161124 IS - 0014-4886 (Print) IS - 0014-4886 (Linking) VI - 202 IP - 1 DP - 2006 Nov TI - Brain-derived neurotrophic factor induces post-lesion transcommissural growth of olivary axons that develop normal climbing fibers on mature Purkinje cells. PG - 44-56 AB - In the adult mammalian central nervous system, reinnervation and recovery from trauma is limited. During development, however, post-lesion plasticity may generate alternate paths providing models to investigate factors that promote reinnervation to appropriate targets. Following unilateral transection of the neonatal rat olivocerebellar pathway, axons from the remaining inferior olive reinnervate the denervated hemicerebellum and develop climbing fiber arbors on Purkinje cells. However, the capacity to recreate this accurate target reinnervation in a mature system remains unknown. In rats lesioned on day 15 (P15) or 30 and treated with intracerebellar injection of brain-derived neurotrophic factor (BDNF) or vehicle 24 h later, the morphology and organisation of transcommissural olivocerebellar reinnervation was examined using neuronal tracing and immunohistochemistry. In all animals BDNF, but not vehicle, induced transcommissural olivocerebellar axonal growth into the denervated hemicerebellum. The distribution of reinnervating climbing fibers was not confined to the injection sites but extended throughout the denervated hemivermis and, less densely, up to 3.5 mm into the hemisphere. Transcommissural olivocerebellar axons were organised into parasagittal microzones that were almost symmetrical to those in the right hemicerebellum. Reinnervating climbing fiber arbors were predominantly normal, but in the P30-lesioned group 10% were either branched within the molecular layer forming a smaller secondary arbor or were less branched, and in the P15 lesion group the reinnervating arbors extended their terminals almost to the pial surface and were larger than control arbors (P < 0.02). These results show that BDNF can induce transcommissural olivocerebellar reinnervation, which resembles developmental neuroplasticity to promote appropriate target reinnervation in a mature environment. FAU - Dixon, Kirsty J AU - Dixon KJ AD - School of Veterinary and Biomedical Sciences, James Cook University, Australia. k.dixon@anhb.uwa.edu.au FAU - Sherrard, Rachel M AU - Sherrard RM LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060621 PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Calbindins) RN - 0 (Dextrans) RN - 0 (Fluoro-Ruby) RN - 0 (Rhodamines) RN - 0 (S100 Calcium Binding Protein G) RN - 0 (Vesicular Glutamate Transport Protein 2) SB - IM MH - Afferent Pathways/pathology MH - Animals MH - Animals, Newborn MH - Axons/*drug effects MH - Brain Injuries/*drug therapy/pathology MH - Brain-Derived Neurotrophic Factor/*therapeutic use MH - Calbindins MH - Cerebellum/*pathology MH - Denervation/methods MH - Dextrans/metabolism MH - Disease Models, Animal MH - Female MH - Immunohistochemistry/methods MH - Male MH - Olivary Nucleus/*pathology MH - Purkinje Cells/*drug effects/physiology MH - Rats MH - Rats, Wistar MH - Rhodamines/metabolism MH - S100 Calcium Binding Protein G/metabolism MH - Vesicular Glutamate Transport Protein 2/metabolism EDAT- 2006/06/23 09:00 MHDA- 2006/12/21 09:00 CRDT- 2006/06/23 09:00 PHST- 2006/03/10 00:00 [received] PHST- 2006/04/12 00:00 [revised] PHST- 2006/05/06 00:00 [accepted] PHST- 2006/06/23 09:00 [pubmed] PHST- 2006/12/21 09:00 [medline] PHST- 2006/06/23 09:00 [entrez] AID - S0014-4886(06)00296-2 [pii] AID - 10.1016/j.expneurol.2006.05.010 [doi] PST - ppublish SO - Exp Neurol. 2006 Nov;202(1):44-56. doi: 10.1016/j.expneurol.2006.05.010. Epub 2006 Jun 21.